Signal transduction pathways leading to spore differentiation in Dictyostelium discoideum.
Cells that overexpress PKA as a consequence of carrying multiple copies of the gene encoding the catalytic subunit can be induced to sporulate when developing as single cells. A peptide phosphorylated by PKA, termed SDF-1, has recently been shown to stimulate this process (Anjard et al., 1997). Several genes have been implicated in a signal transduction pathway by which prestalk cells induce encapsulation of prespore cells during terminal differentiation including a prestalk-specific putative membrane protease (TagC) and a two-component system consisting of a receptor-histidine kinase (DhkA) and a response regulator with cAMP phosphodiesterase activity (RegA). To determine whether SDF-1 uses this pathway, strains carrying null mutations in the pertinent genes were transformed with a pkaC plasmid such that they can overexpress PKA. Since these mutant strains all sporulated efficiently when SDF-1 was added, it appears that other gene products mediate the response. However, we found that regA- mutant cells release a distinct factor, SDF-2, that rapidly induces encapsulation of test cells overexpressing pkaC. Since cells in which tagC is disrupted do not form SDF-2 and cells in which dhkA is disrupted do not respond to SDF-2, this peptide appears to use the two-component system that regulates PKA activity. SDF-2 is a small peptide released by prestalk cells in a manner dependent on TagC. It appears to act on prespore cells through the DhkA receptor to inhibit the cAMP phosphodiesterase of RegA, thereby activating PKA via cAMP. The process of induction by SDF-2 can be shown to be distinct from that by SDF-1. SDF-2 appears to stimulate prestalk cells to release additional SDF-2 by acting through a signal transduction pathway that also involves DhkA, RegA, and PKA. Based on these results we present a model for the signal transduction cascade regulating spore differentiation.
Anjard
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C
Department of Genetics, Kassel University, Germany.
Zeng
C
C
Loomis
W F
WF
Nellen
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D000818:Animals; D002478:Cells, Cultured; D054377:Chemokine CXCL12; D018925:Chemokines / Q000096:biosynthesis / Q000502:physiology; D019743:Chemokines, CXC; D017868:Cyclic AMP-Dependent Protein Kinases / Q000502:physiology; D004023:Dictyostelium / Q000201:enzymology / Q000235:genetics / Q000254:growth & development*; D010450:Endopeptidases / Q000502:physiology; D005656:Fungal Proteins / Q000502:physiology; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000378:metabolism; D009154:Mutation; D010455:Peptides; D011494:Protein Kinases / Q000502:physiology; D011506:Proteins / Q000502:physiology; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D013172:Spores, Fungal / Q000235:genetics / Q000254:growth & development
D054377:Chemokine CXCL12; D018925:Chemokines; D019743:Chemokines, CXC; D005656:Fungal Proteins; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D010455:Peptides; D011506:Proteins; C484455:SDF-2 protein, Dictyostelium discoideum; D011494:Protein Kinases; D017868:Cyclic AMP-Dependent Protein Kinases; C101160:DhkA protein, Dictyostelium discoideum; D010450:Endopeptidases